Neurological aspects of del(1q) syndrome

We have studied three children with de novo terminal deletion of the long arm of chromosome 1 (46,XX,del(1)(q43)). They all have minor anomalies and neurological signs (severe psychomotor developmental delay, generalized hypotonia, and seizures) that have been described previously. In addition, all of these three patients have autistic-like behavior. They avoid eye contact, show no interest in people, express little emotion, and repeat stereotypic movements such as head nodding and purposeless finger manipulation. They also spend excessive time in making unusual sounds consisting of a high-pitched shrill cry with little intonation in infancy and a harsh, strained, and glottal stridency in later life. They make no labial, lingual, or nasal sounds. We suggest that these observations may be unique clinical manifestations of certain terminal 1q deletions.     

Prevention for preschoolers at high risk for conduct problems: immediate outcomes on parenting practices and child social competence.

This study investigated the immediate impact of an 8-month center- and home-based prevention program for preschoolers at high risk for conduct problems. We report immediate program effects on observed and self-rated parenting practices and observed child behavior with peers. Ninety-nine preschool-age siblings of adjudicated youths and their families were randomly assigned to an enhanced version of the Incredible Years Series (Webster-Stratton, 1989; n = 50) or to a no-intervention control condition (n = 49). In an intent-to-treat design, the intervention yielded significant effects on negative parenting, parental stimulation for learning, and child social competence with peers. Improvements in negative parenting, stimulation for learning, and child social competence support the potential of the intervention to prevent later conduct problems in high-risk children.     

Does the myosin V neck region act as a lever?

Recent research efforts from several groups have addressed the question of whether the amplitude of myosin's unitary step size is proportional to the length of the neck region. Unconventional myosin V, which has an extended neck region with 6IQ motifs, provides a natural template by which to test the lever arm model via mutational analysis. The most stringent test requires that a series of single-headed molecules from the same myosin class be analyzed. Here we characterized the unitary mechanics of three single-headed fragments of myosin V expressed in the baculovirus/insect cell system. Each construct consisted of the motor domain (MD) and a variable number of IQ motifs (MD2IQ, MD4IQ and MD6IQ) that bind calmodulin, followed by an epitope tag so that the molecule can be attached to the nitrocellulose surface via an antibody. The results show a correlation between the unitary step size and the number of IQ motifs, confirming that the myosin neck region acts as a lever. The step size of MD2IQ is twice that observed from single-headed subfragments of class II myosins with the same neck length. Our results are discussed in relation to data obtained concurrently from other laboratories with similar constructs.     

Latency of multiple skin conductance responses in differential classical conditioning

Latencies of multiple skin conductance responses were observed in 30 female undergraduate students who participated in a classical differential conditioning experiment employing a 10 sec interstimulus interval (ISI). Responses occuring in both the early and late portions of the ISI were examined. Pairing delayed the onset of early responses and hastened the onset of responses occuring later in the ISI. Additionally, the latency changes observed did not appear to be an artifact of the higher response frequencies typically associated with conditioning.     

Fear-Potentiated Startle in Humans: Effects of Anticipatory Anxiety on the Acoustic Blink Reflex

The effects of fear/anticipatory anxiety on the acoustic startle reflex were investigated in humans using a paradigm involving anticipation of electric shocks. The eyeblink component of the startle reflex, elicited by an abrupt auditory stimulus, was measured in 9 normal volunteers during either the anticipation of electric shocks (anticipatory anxiety) or periods in which no shocks were anticipated (safe period). The eyeblink was consistently higher in amplitude, and shorter in latency, during periods when the subjects anticipated shocks, compared to the safe periods. This effect could not be attributed solely to a reduction in habituation and was statistically significant before the subjects actually received any shock (a single 30 mA stimulation on the median nerve). These results indicate that anticipatory anxiety can be measured objectively in humans using the fear-potentiated startle reflex in a paradigm not actually requiring any shock. Because a great deal is known about the neuroanatomical and pharmacological mechanisms of fear-potentiated startle in laboratory animals, this test procedure may be especially useful in humans to investigate the neurobiological substrates of anxiety disorders and their pharmacological treatments.     

Defect in the tissue cellular immune response: experimental visceral leishmaniasis in euthymic C57BL/6 ep/ep mice.

In BALB/c mice, successful defense against visceral leishmaniasis is T cell dependent, expressed by tissue granuloma formation, and probably mediated by macrophages activated by cytokines, including gamma interferon (IFN-gamma). C57BL/6 ep/ep (pale ear) mice, which reportedly exhibit impaired IFN-gamma production, were challenged with Leishmania donovani to determine the outcome of infection in a euthymic host with an apparent defect in lymphokine secretion. In BALB/c and normal C57BL/6 mice, L. donovani liver burdens peaked at 2 weeks and were largely eliminated by 4 weeks. In contrast, in pale ear mice, infection progressed until after 4 weeks and persisted at high levels at 8 weeks. The failure to resolve hepatic infections was not related to deficiencies in (i) Thy-1+, L3T4+, or Lyt-2+ T cells; (ii) IFN-gamma secretion; (iii) liver tissue Ia expression; (iv) macrophage antimicrobial capacity; or (v) antileishmanial antibody production. However, despite the anticipated influx of mononuclear cells into livers, these cells were not properly focused on the parasitized Kupffer cells, the inflammatory infiltrate receded prematurely, and mature granulomas failed to develop. These results suggest that there is a cellular immune defect at the tissue level and emphasize the critical role of granuloma formation in successful resolution of systemic intracellular infections.     

Correlates of sensitization to Blomia tropicalis and Dermatophagoides pteronyssinus in asthma in Barbados

BACKGROUND: Sensitivity to the mite Blomia tropicalis is related to asthma in tropical climates, but correlates of sensitivity to B. tropicalis and its relationship to Dermatophagoides pteronyssinus sensitivity have not been widely examined in families with asthma. The main objective of this study was to determine prevalence and correlates of sensitivity to these mites in families with asthma and characteristics of persons sensitized to both. METHODS: Antibodies to major antigens (Blo t 5 and Der p 1) of these mites were measured by immunochemiluminescent assay in 481 members of 29 families from Barbados ascertained through two asthmatic siblings. RESULTS: Blo t 5 sensitivity was present in 261 subjects (46%) and was associated with younger age, higher total serum IgE level, and more than a three-fold increased prevalence of asthma (42 vs. 13%). Der p 1 sensitivity was less common (27%) and showed similar associations with age, IgE, and asthma. Of the 261 subjects sensitized to Blo t 5, 116 were also sensitized to Der p 1; they were younger, had higher total and Blo t 5 specific IgE levels, and had more than twice the asthma prevalence as those sensitized to Blo t 5 alone (59 vs. 29%). Der p 1 sensitivity without Blo t 5 sensitivity was uncommon; 90% of those sensitized to Der p 1 were also sensitized to Blo t 5. Geometric mean total IgE levels were lowest in the 207 participants without any mite sensitization (102 U/ml), intermediate in 158 sensitized to either Blo t 5 OR Der p 1 (609 U/ml), and highest in 116 sensitized to both (1,869 U/ml). CONCLUSIONS: Blo t 5 is the predominant sensitizing mite allergen in these Barbadian families with correlates similar to Der p 1. Concomitant sensitization to Der p 1 appears to identify a more reactive subgroup of individuals at a higher risk of asthma.     

Millon Clinical Multiaxial Inventory-III subtypes of opioid dependence: validity and matching to behavioral therapies

The concurrent and predictive validity of 2 different methods of Millon Clinical Multiaxial Inventory-III subtyping (protocol sorting, cluster analysis) was evaluated in 125 recently detoxified opioid-dependent outpatients in a 12-week randomized clinical trial. Participants received naltrexone and relapse prevention group counseling and were assigned to 1 of 3 intervention conditions: (a) no-incentive vouchers, (b) incentive vouchers alone, or (c) incentive vouchers plus relationship counseling. Affective disturbance was the most common Axis I protocol-sorted subtype (66%), antisocial-narcissistic was the most common Axis II subtype (46%), and cluster analysis suggested that a 2-cluster solution (high vs. low psychiatric severity) was optimal. Predictive validity analyses indicated less symptom improvement for the higher problem subtypes, and patient treatment matching analyses indicated that some subtypes had better outcomes in the no-incentive voucher conditions.